Chondroitin sulfate is a kind of glycosaminoglycans, which is a polysaccharide having a backbone in which a disaccharide resulting from the bonding of glucuronic acid and N-acetylgalactosamine via 1-3 glycosidic linkage is connected in a row via 1-4 glycosidic linkage (hereinafter also referred to as “basic backbone”) and having sulfate groups.
In addition to the glycosaminoglycans such as chondroitin sulfate, in many cases, proteoglycans, glycoproteins and glycolipids have sulfate groups, and many types of sulfotransferases relate to their biosyntheses. Particularly, it has been suggested that the enzyme described in J. Biol. Chem., 276, 43894-43900 (2001), chondroitin sulfate formed thereby (J. Biol. Chem., 264, 14916-14922 (1989)) and the like deeply relate to the immune system, nervous system or inflammatory reactions, and inhibitors of the enzymes have a high possibility of being able to apply to an immunosuppressive agent (e.g., therapeutic agent for atopic dermatitis, asthma and Crohn disease, etc.) and a nerve controlling agent and a disease treating agent (e.g., therapeutic agent, nerve repair controlling agent, anti-inflammatory agent, etc. for neurosis, Alzheimer disease, maniac-depressive psychosis, psychosis, autonomic imbalance, nervous enteritis, etc.) (U.S. Pat. Nos. 6,265,192, 6,365,365, etc.).
As such sulfotransferase inhibitors, for example, the chlorate described in Biochem. Biophys. Res. Commun., 150, 342-348 (1988), the brefeldin A described in J. Biol. Chem., 267, 8802-8806 (1992) and the like are present. However, since the former shows nonspecific antagonism upon the sulfate group transfer by a sulfotransferase, and the latter destroys the Golgi body which is the field of sugar chain synthesis, they have activity of strongly inhibiting biosynthesis of not only chondroitin sulfate but also other glycosaminoglycans and glycoproteins, so that their possibility to be used as therapeutic agents was extremely low.
Accordingly, concern has been directed toward a novel compound having highly specific inhibitory activity for a specified sulfotransferase, and a novel sulfotransferase inhibitor which uses the same.